Survival in stage I-III breast cancer patients by surgical treatment in a publicly funded health care system.

BACKGROUND: Recent investigations of breast cancer survival in the United States suggest that patients who receive mastectomy have poorer survival than those who receive breast-conserving surgery (BCS) plus radiotherapy, despite clinically established equivalence. This study investigates breast cancer survival in the publicly funded health care system present in Alberta, Canada. PATIENTS AND METHODS: Surgically treated stage I-III breast cancer cases diagnosed in Alberta from 2002 to 2010 were included. Demographic, treatment and mortality information were collected from the Alberta Cancer Registry. Unadjusted overall and breast cancer-specific mortality was assessed using Kaplan-Meier and cumulative incidence curves, respectively. Cox proportional hazards models were used to calculate stage-specific mortality hazard estimates associated with surgical treatment received. RESULTS: A total of 14 939 cases of breast cancer (14 633 patients) were included in this study. The unadjusted 5-year all-cause survival probabilities for patients treated with BCS plus radiotherapy, mastectomy, and BCS alone were 94% (95% CI 93% to 95%), 83% (95% CI 82% to 84%) and 74% (95% CI 70% to 78%), respectively. Stage II and III patients who received mastectomy had a higher all-cause (stage II HR = 1.36, 95% CI 1.13-1.48; stage III HR = 1.74, 95% CI 1.24-2.45) and breast cancer-specific (stage II HR = 1.39, 95% CI 1.09-1.76; stage III HR = 1.79, 95% CI 1.21-2.65) mortality hazard compared with those who received BCS plus radiotherapy, adjusting for patient and clinical characteristics. BCS alone was consistently associated with poor survival. CONCLUSIONS: Stage II and III breast cancer patients diagnosed in Alberta, Canada, who received mastectomy had a significantly higher all-cause and breast cancer-specific mortality hazard compared with those who received BCS plus radiotherapy. We suggest greater efforts toward educating and encouraging patients to receive BCS plus radiotherapy rather than mastectomy when it is medically feasible and appropriate.

Thalamofrontal neurodevelopment in new-onset pediatric idiopathic generalized epilepsy.

BACKGROUND: Quantitative MRI techniques have demonstrated thalamocortical abnormalities in idiopathic generalized epilepsy (IGE). However, there are few studies examining IGE early in its course and the neurodevelopmental course of this region is not adequately defined. OBJECTIVE: We examined the 2-year developmental course of the thalamus and frontal lobes in pediatric new-onset IGE (i.e., within 12 months of diagnosis). METHODS: We performed whole-brain MRI in 22 patients with new-onset IGE and 36 age-matched healthy controls. MRI was repeated 24 months after baseline MRI. Quantitative volumetrics were used to examine thalamic and frontal lobe volumes. RESULTS: The IGE group showed significant differences in thalamic volume within 1 year of seizure onset (baseline) and went on to show thalamic volume loss at a significantly faster rate than healthy control children over the 2-year interval. The control group also showed a significantly greater increase in frontal white matter expansion than the IGE group. In contrast, frontal lobe gray matter volume differences were moderate at baseline and persisted over time, indicating similar developmental trajectories with differences early in the disease process that are maintained. CONCLUSIONS: Brain tissue abnormalities in thalamic and frontal regions can be identified very early in the course of IGE and an abnormal trajectory of growth continues over a 2-year interval.

Synoptic operative record for point of care outcomes: a leap forward in knowledge translation.

INTRODUCTION: Modern information technology coupled with synoptic methodology allows point of care, real time outcomes generation. Our objective was to review province-wide breast cancer surgery outcomes from a prospective synoptic operative record to demonstrate its value in knowledge translation. METHODS: All synoptic reports for breast cancer procedures from 2006 until March 2010 were reviewed and descriptively analyzed. Key outcomes included frequency of breast cancer procedures captured over time, methods of breast cancer detection, clinical staging, method of axillary staging, breast conservation and reconstruction rates. Further analysis involved important decision-making for mastectomy and resource allocation for surgery. RESULTS: Four thousand nine hundred fifty-five breast cancer procedures were recorded synoptically; greater than 80% of cases provincially. Method of breast cancer detection was 49%, 45% and 4% by screening radiology, patient or family, and physician, respectively. Pathologic diagnoses were via core or mammotome biopsy in 94%; nearly half of all patients were clinical Stage I at time of operation. Overall rate of breast conservation was 48%. Of the 65% who had no contra-indication to breast conservation surgery, 76% had breast conservation and 4% had primary reconstruction. Of those having mastectomy, one third were due to patient choice. Seventy-nine percent had sentinel node staging, 18% had full axillary dissection and 3% had no axillary staging. CONCLUSION: A new paradigm of creating medical records using synoptic electronic templates allows prospective outcomes generation at point of care by the surgeon which is unparalleled in its depth of surgical detail capturing surgical decision-making.

Production of [17F]CH3F (t1/2=65 s), an improved PET tracer for rCBF measurement.

Production of 17F (t1/2=65 s) in the form of [17F] F2 has been achieved using both the 20Ne(p,alpha)17F and 16O(d,n)17F reactions with 11 MeV protons and 6 MeV deuterons, respectively. Yields have proven suitable for subsequent radiosynthesis of the blood flow tracer, [17F]CH3F (>60 mCi in saline), currently in use for fast repetition human studies of regional cerebral blood flow with positron emission tomography. Thick target yields of 15 mCi /microA for protons and 44 mCi/microA for deuterons have been measured for [17F]F2.

Water-cooled grid support for high-power irradiation with thin target windows.

A new thin window support system for the accelerator production of positron emitters (e.g. 17F, 18F 11C, 15O) has been developed. The integrated support grid and cooling design has been optimized for 6-13 MeV protons or deuterons. The water-cooled support grid regularly operated at > 100 microA of 6 MeV deuterons and protons. The grid performed without failure at > or = 50 microA of 13 MeV protons on a 3.1 MPa gas target using 25.4 microm aluminum target foil. Transmission for the smallest hole grid of 72% based on uniform parallel beam agreed with the measured yield of 71 +/- 1% compared to the theoretical maximum yield.

Improved survival of in vitro cultured canine islet allografts.

Pure islets transplanted from single donors survive in outbred dogs when CsA is administered at high doses (15-20 mg/kg/day), but not report has documented prolonged function with less CsA. In this study, we investigated survival of canine islets that were immunomodulated with in vitro culture and transplanted with minimal CsA. Highly purified islets from single donors (n = 17) were cultured in vitro at 22 degrees C for 7 days. Four groups of apancreatic, outbred mongrel dogs received islets into the spleen: group 1 (n = 4), fresh islet controls; group 2 (n = 5), cultured islet controls; group 3 (9033 +/- 994 islets/kg, n = 12), culture and CsA; group 4 (9050 +/- 1091 islets/kg, n = 8), fresh islet and CsA. CsA was administered in doses of 5-8 mg/kg/day to maintain whole blood trough levels of 300-500 ng/ml. At 30 days after implant, the CsA was stopped. After 7-day culture, 80% of the endocrine mass was recovered. All grafts restored plasma glucose to < 150 mg/dl. Group 1 and 2 dogs became hyperglycemic at 5 +/- 1 (+/- SE) and 6 +/- 1 days. Three grafts in group 3 failed when CsA did not reach target blood levels. Of the 9 dogs with CsA levels of 300-500 ng/ml, 1 died at 9 days while normoglycemic, and the remainder were normoglycemic for 35.5 +/- 8.3 days (median 38 days). Seven group 4 dogs with these CsA levels achieved normoglycemia for 7.7 +/- 1.9 days (median 9 days, survival vs. group 3, P = 0.03, by Mann-Whitney test). In vitro tissue culture of mass quantities of single-donor allogeneic islets enhances their survival with low dose immunosuppression in outbred diabetic dogs.

Comparison of automated and manual methods for islet isolation.

The authors used the principal features of a collagenase perfusion technique and an automated dissociation technique to determine if islets could be isolated from the large mammal pancreas and to compare the effects of the two methods on isolated islets. The pancreases of 16 dogs were cannulated and perfused with collagenase at 4 degrees C, then warmed to 37 degrees C. Group 1 (eight) pancreases were perfused at 37 degrees C until digested, then dissociated manually by teasing and trituration. Group 2 (eight) pancreases were transferred to a closed chamber for continued collagenase digestion and dissociation at 37 degrees C. Islets were purified using identical Ficoll gradients. Aliquots were stained with dithizone and evaluated for number, size and purity. Total islet volume was calculated. Group 2 pancreases were thoroughly digested leaving only a few residual ducts, but undigested fragments persisted in group 1 pancreases. Islet size was similar in both groups. There was a greater islet volume before and after Ficoll purification in group 2, but the difference was not significant. Purity was greater than 90% in both groups. Perifusion with 28 mM glucose elicited a biphasic insulin release from islets in both groups. The data show that the combined protocol enables mass isolation of purified islets from the canine pancreas. Compared with the manual technique, the automated protocol for pancreas dissociation tends to improve the yield of islets without compromising islet size and viability. It provides the advantages of a closed system with increased control over the extent of collagenase digestion.

Critical mass of islets that function after implantation in a large mammalian.

A major problem that limits clinical islet transplantation is insufficient information on the critical quantity of islets needed to reverse insulin dependence. To address this problem, we have previously identified the critical number of purified islets of known size that consistently induced normoglycemia in a large mammal model of type I diabetes. In the present studies, we found that the dose-response relationship between the volume of islets transplanted and consistent normoglycemia in dogs corresponded to greater than 4.1 microliters islet tissue per kilogram body weight. The functional outcome of similar quantities of purified islets was then examined after autoimplantation into splenic or hepatic sites and after splenic implantation by venous reflux or pulp injection. During prolonged follow-up, four of five initially normoglycemic recipients of intrahepatic islets became hyperglycemic within 1 year and the other failed at 26 months. In contrast, function of intrasplenic islets was more durable with delayed onset of hyperglycemia observed in only two of six grafts at 13 and 18 months. Sustained normoglycemia was induced by splenic venous reflux of islets in six of seven dogs, but intrapulp injection succeeded in only two of six. Islet allografts implanted to the spleen (n = 10) or to the kidney capsule (n = 6) of Cyclosporine-treated recipients induced normoglycemia in all, but sustained function ensued in only the intrasplenic group when the islet mass was augmented by 40%. These data define the critical islet volume needed to induce normoglycemia in a large mammal. Islets implanted by venous reflux to spleen provide more durable long-term function than the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral breast cancer in northern Alberta: risk factors and survival patterns.

Of 2231 women with stage I, II or III breast cancer who were registered and seen between 1971 and 1979 and followed to the end of 1981, 48 (2.2%) had synchronous and 58 (2.6%) asynchronous bilateral breast cancer. The unadjusted incidence rate for a second breast cancer was 6.4/1000 breast-years at risk, compared with a rate of 0.70 for the risk of a first breast cancer in women. When calculated from the date of diagnosis of the first breast cancer the survival rate was better for the group with asynchronous disease than for the group with synchronous disease or for a group with unilateral disease, but when calculated from the date of diagnosis of the second cancer the rate was the same in all three groups. Comparison of known risk factors showed a significant association between the development of bilateral cancer and a later age at the birth of the first child and a longer interval between menarche and that birth. There was a trend towards greater age and more stage III cancer in the group with synchronous disease. There was no correlation between receiving radiotherapy for the first breast cancer and development of the second cancer. Annual mammography and clinical examination of asymptomatic women at a cancer centre resulted in the detection of a significantly higher proportion of minimal breast cancers in the second breast compared with the first. Such screening practices should be even more valuable in the earlier detection of unilateral breast cancer in asymptomatic women who have not had breast cancer.

Family planning hotline.

PIP: Since last March, a family planning hotline has been putting the caller in touch with the Family Planning Information Service. This is possibly the 1st centralized referral and information service for family planning in any major city in the U.S. Each months this fall 1400 New Yorkers called the hotline number to obtain information about family planning, infertility, abortion, and voluntary sterilization. Several major parallel developments made the creation of the Family Planning Information Service possible and strengthened its changes of success. The service is headed by a registered nurse who is assisted by 2 specially trained nonprofessional staff members. The unit is housed in Planned Parenthood's Manhattan headquarters. The Service has a special telephone number which is listed in all telephone directories. A number of promotional devices have been used to build and maintain the volume of inquiries. The results of the intensive work to develop and maintain the service have been dramatic. From a monthly volume of 300 calls in March, the figure in May had reached 670. In July there were 962 inquiries and in October the figure rose to 1421. About 90% of these calls are from women. By far the largest number of requests for information have concerned contraception and where such services can be obtained. Over 200 calls have been inquires about infertility problems, and 361 calls have concerned abortion. More than 100 calls have been about sterilization, with men outnumbering women 2:1.^ieng